Gastrointestinal pH profiles in patients with inflammatory bowel disease

BACKGROUND: 5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating. AIM: To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen. METHODS: Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn's disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease). RESULTS: The median gastric pH values in the patient groups (Crohn's disease 2.4, range 1.5-4.1; ulcerative colitis 1.95, range 1.55-4.4) were significantly higher than those observed in the controls (1.55, range 0.95-2.6). In the small bowel and colonic segments, all the pH values of Crohn's disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission. CONCLUSIONS: The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.     

The surgical management of nonspecific inflammatory bowel disease: a small personal experience

AIMS: To document the surgical management of patients with non specific inflammatory bowel disease managed in the colorectal service, University Department of Surgery, Wellington School of Medicine. METHODS: Retrospective analysis of patients managed between April 1975 and March 1990. RESULTS: Sixty five patients had inflammatory bowel disease. Twenty one (11 males) had ulcerative colitis and 44 (18 males) had Crohn's disease. There were no Maori. One hundred and twenty three operations were performed overall. Ten patients with ulcerative colitis were operated upon as emergencies. Five presented with fulminating disease. Six patients successfully underwent restorative proctocolectomy although one was subsequently thought to have had Crohn's disease. Overall there was one postoperative death. Crohn's disease patients underwent a total of 91 operations. Twenty nine operations were elective and 15 emergency during the first surgical admission. The commonest indication for surgery was stricture. The commonest operation performed was right hemicolectomy. Chest, wound and central line sepsis were the commonest postoperative problems. There were two postoperative deaths. Six patients favoured a series of relatively minor perineal operations to proctectomy. CONCLUSION: A cautious staged approach to the surgical management of inflammatory bowel disease patients resulted in only three deaths-an overall mortality rate of 4.6%. Accordingly we advocate a policy of expectant surgery to relieve symptoms or correct complications in patients with Crohn's disease. We believe that patients requiring surgery for ulcerative colitis should be offered the choice of either restorative proctocolectomy or panproctocolectomy and ileostomy.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

Epitope mapping of cytochrome P450cam (CYP101)

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.     

Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.     

Pericarditis in chronic inflammatory bowel disease: underlying disease or side effects of therapy? Clinical problem solving

Pericarditis and myocarditis are rare extraintestinal manifestations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease). Pericarditis as a side effect induced by sulfasalazine or 5-aminosalicylic acid, drugs used in the therapy of these diseases, was first described only 7 years ago. In older case reports the relationship between the use of these drugs and pericarditis is unclear. We analyze the reported cases of 68 patients (38 men, 24 women) with ulcerative colitis (n = 45) or Crohn's disease (n = 15) who had one or more episodes of pericarditis or myopericarditis. Pericarditis was not associated with high activity of bowel disease in all cases. In most cases therapy with corticosteroids led to uneventful recovery. In drug induced pericarditis omission of the 5-ASA therapy was sufficient in a few cases. There was one fatal case (with myocarditis). The decision whether pericarditis is a symptom of the underlying disease or a side effect of the drug used for the treatment of the disease is not always easy. We present an analysis (clinical problem solving) of a pertinent observation in a patient with Crohn's disease and pericarditis, showing the dilemma of pericarditis in chronic inflammatory bowel disease and its therapy.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Crohn's colitis: the fate of the rectum

Previous reports suggest that up to 70% of patients undergoing surgery for Crohn's disease of the large bowel do not have gastrointestinal continuity restored and require a permanent ileostomy. In this study the experience with patients requiring surgical treatment of large bowel Crohn's disease is reviewed with particular reference to the management of the rectum. The records of 19 elective and 25 urgent colonic resections performed for large bowel Crohn's disease in 44 patients (16 males, 28 females; mean age 41 years, range 17-76) between 1983 and 1995 were reviewed. Staged proctectomy was performed in 5 of 12 patients who had colectomy for acute colitis and in one patient who had had an elective colectomy. Permanent ileostomy was required in 72% of patients with acute Crohn's colitis and 84% of patients who had elective surgery for large bowel Crohn's. Over 70% of patients having surgical treatment of Crohn's disease of the large bowel required permanent ileostomy. No cases of cancer developed in patients with retained rectal stumps.     

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: diagnostic tool or research procedure?

Antineutrophil cytoplasmic antibodies, initially detected in the sera of patients with Wegener's granulomatosis and other forms of systemic vasculitides, have also been observed in patients with inflammatory bowel disease, with a higher prevalence in ulcerative colitis. In this study, we investigated the prevalence of these antibodies in the sera of 42 patients with ulcerative colitis and 48 patients with Crohn's disease, and the possible correlations with disease activity and extent, extraintestinal complications, and therapy. Antineutrophil cytoplasmic antibodies were found in 30 out of the 42 patients with ulcerative colitis (71.4%); only 16 out of the 48 patients (33.3%) with Crohn's disease were positive (p < 0.001), and the prevalent pattern was perinuclear. No correlations with disease activity and extent, extraintestinal complications, or surgical or medical treatment were found. Our data indicate that in the case of inflammatory bowel disease, the search for antineutrophil cytoplasmic antibodies still remains a research procedure and cannot be used for clinical diagnosis.     

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.     

Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews

The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non-Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models.     

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.     

Direct detection of Mycobacterium tuberculosis complex and M. avium complex in tissue specimens from cattle through identification of specific rRNA sequences

BACKGROUND: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany. PATIENTS AND METHODS: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients). RESULTS: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis. CONCLUSION: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Sonography of inflammatory bowel disease: findings and value in differential diagnosis

OBJECTIVE: Inflammatory bowel diseases produce segmental or diffuse mural thickening of the intestine that can be detected and evaluated by using sonography. The purpose of this study was to evaluate the sonographic findings and determine their diagnostic value in patients with inflammatory bowel diseases. MATERIALS AND METHODS: We reviewed sonograms of 81 patients with inflammatory bowel diseases. The findings were compared with those of barium study, colonoscopy, and surgery. Forty-five patients had tuberculous enterocolitis, 13 had ulcerative colitis, eight had Crohn's disease, five had ischemic colitis, two had Beh?et's syndrome, and eight had unspecified colitis. Diagnosis was based on surgical and pathologic findings in 23; results of barium study and endoscopic biopsy in 20; and results of barium study, colonoscopic findings, and clinical findings in 38. RESULTS: Seventy-two patients (89%) had sonograms that showed segmental or diffuse mural thickening and a paucity of luminal content in the involved bowel. Involved areas were the ileocecal region in the cases of tuberculous enterocolitis and Beh?et's syndrome, the left side of the colon in ulcerative colitis, and the colon and terminal part of the ileum in Crohn's disease. In ischemic colitis, the distribution of involved bowel was nonspecific. Sonographic findings correlated well with the findings of barium enema or colonoscopy in terms of the involved segments of the bowel. Mesenteric lymphadenitis, omental thickening, and ascites were frequently observed in cases of tuberculous enterocolitis. CONCLUSION: Sonographic evidence of mural thickening of the bowel with a paucity of luminal content may be helpful in the detection of inflammatory bowel diseases. However, the findings are nonspecific, and the differential diagnosis must be related to the specific segment of the bowel involved.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

An increased risk of Crohn's disease in individuals who inherit the HLA class II DRB3*0301 allele

The role of inflammatory T cells in Crohn's disease suggests that inherited variations in major histocompatibility complex (MHC) class II genes may be of pathogenetic importance in inflammatory bowel disease. The absence of consistent and strong associations with MHC class II genes in Caucasian patients with inflammatory bowel disease probably reflects the use of less precise typing approaches and the failure to type certain loci by any means. A PCR-sequence-specific oligonucleotide-based approach was used to type individual alleles of the HLA class II DRB1, DRB3, DRB4, and DRB5 loci in 40 patients with ulcerative colitis, 42 Crohn's disease patients, and 93 ethnically matched healthy controls. Detailed molecular typing of the above alleles has previously not been reported in patients with inflammatory bowel disease. A highly significant positive association with the HLA-DRB3*0301 allele was observed in patients with Crohn's disease (P = 0.0004) but not in patients with ulcerative colitis. The relative risk for this association was 7.04. Other less significant HLA class II associations were also noted in patients with Crohn's disease. One of these associations involved the HLA-DRB1*1302 allele, which is known to be in linkage disequilibrium with HLA-DRB3*0301. These data suggest that a single allele of an infrequently typed HLA class II locus is strongly associated with Crohn's disease and that MHC class II molecules may be important in its pathogenesis.